Effective delivery of genome editor to cervical cancer targeting Mcl1 for cancer therapy

Sep 22, 2026

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CRISPR/Cas9 enables precise, targeted genome editing, but broad clinical use is limited by off-target activity and insufficient delivery of editing tools. This study engineers an endogenic extracellular vesicle (EVs) system to deliver Cas9 ribonucleoprotein (RNP) effectively. Endogenic Cas9 RNP are sorted via Lamp2b and delivered by engineered EVs, inducing apoptosis and suppressing cervical cancer cell growth. The EVsRNP complex (Cas9-Mcl1) further achieves strong antitumor effects in cervical cancer animal models by downregulating Mcl1 expression, indicating a promising delivery strategy for cancer therapy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

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ARTICLE OPEN

Graphical Abstract

INTRODUCTION

[www.nature.com/cgt](www.nature.com/cgt) Cancer Gene Therapy ARTICLE OPEN Effective delivery of genome editor to cervical cancer targeting Mcl1 for cancer therapy Yue Wan1, Yiming He2, Xun Chen1, Shengwu Wang 1, Guannan Zhou 1,3,4 ✉, Xiaoyan Ying2,4 ✉ and Haiyan Zhang 1,4 ✉ © The Author(s) 2026 | | | | | --- | --- | --- | | | CRISPR/Cas9 represents a transformative advancement in precision therapies, offering the promise of more effective and targeted treatment options. However, there are still limitations (including off-target editing as well as unsatisﬁed delivery tool) which obstruct the wide application of CRISPR/Cas9 . Here, an endogenic artiﬁcial extracellular vesicles (EVs) system is engineered for effective delivery of Cas9 ribonucleoprotein (RNP) . We demonstrated that the endogenic Cas9 RNP were sorted by the Lamp2b and delivered by the artiﬁcial EVs, which could markedly inhibit the growth of cervical cancer cells by inducing cell apoptosis. Moreover, artiﬁcial endogenic EVsRNP (Cas9-Mcl1) could result in remarkable antitumor effects in animal models of cervical cancer through suppressing Mcl1 expression. Our ﬁndings indicate that the artiﬁcial EVs delivery strategy could deliver Cas9 RNP effectively to inhibit cancer progression, which might be a promising treatment.
Cancer Gene Therapy (2026) 33:378–389; [https://doi.org/10.1038/s41417-025-00958-w](https://doi.org/10.1038/s41417-025-00958-w) | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Graphical Abstract~~ ~~ Schematic illustration of Cas9 RNP delivery for targeting therapy. (A) The schematics for detecting the Mcl1 expression in cervical cancer from TCGA dataset and patients’ samples; (B) The recombinant “Lamp2b-PhoCl-Cas9” plasmid was constructed and transfected with HEK- 293T. Lamp2b protein was expressed transmembrane of the EVs while Cas9 RNP were encapsulated into EVs; (C) The PhoCl protein could release Cas9 RNP freely into the EVs; (D) EVsRNP (Cas9-Mcl1) could deliver the (Cas9-Mcl1) RNP into the cervical cancer and suppress the cancer progression through editing the Mcl1 expression in cervical cancer. INTRODUCTION Gene editing could modify the targeted genome in a precisely and permanently manner through DNA-binding sequence-speciﬁcnucleases [1] . Gene editing allows for precise and permanent modiﬁcations to the targeted genome using DNA-binding, sequence-speciﬁc nucleases. Among the various tools developed for genome editing, the CRISPR/Cas system has emerged as the most widely adopted and inﬂuential technology worldwide [2] . Its ability to target speciﬁc genes and make alterations with remarkable precision has revolutionized ﬁelds such as genetics, biotechnology, and medicine. In recent years, CRISPR/Cas technology has gained signiﬁcant traction, particularly with the approval 1Department of Gynecology, Sir Run Run Hospital, Nanjing Medical University, Long Mian Avenue 109 Jiangning, Nanjing, Jiangsu, China. 2Department of Obstetrics and Gynecology, Second Afﬁliated Hospital of Nanjing Medical University, No. 262 North Zhongshan Road, Nanjing 210000 Jiangsu Province, China. 3Department of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, 419 Fang-Xie Road, Shanghai 200011, China. 4These authors contributed equally: Guannan Zhou, Xiaoyan Ying, Haiyan Zhang. ✉ email: [zgnsmmu@163.com](zgnsmmu@163.com); [xiaoyanying_cool@163.com](xiaoyanying_cool@163.com); [zhydnj@163.com](zhydnj@163.com) Received: 10 September 2024 Revised: 8 August 2025 Accepted: 1 September 2025 Published online: 27 January 2026 of gene therapy methods based on this system to treat genetic diseases such as sickle cell anemia. The success of these therapies has sparked a renewed interest in the potential of CRISPR/Cas to treat a wide range of genetic disorders, highlighting its transformative potential in the realm of medical science. With approvement of the gene Therapy

FAQs

What main delivery challenge does the study address for CRISPR/Cas9 therapy?

It targets the limitation of delivering CRISPR components such as Cas9 and guide RNA efficiently and specifically into target cells without unacceptable risks.

How are Cas9 RNP delivered in this work?

An engineered endogenic extracellular vesicle (EVs) system sorts Cas9 RNP via Lamp2b and encapsulates the RNP for delivery to cervical cancer cells.

What therapeutic effect is reported against cervical cancer?

Delivered EVs carrying Cas9 RNP (Cas9-Mcl1) markedly inhibit growth by inducing apoptosis and suppress Mcl1 expression, producing antitumor effects in animal models.

Sep 22, 2026

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